Potatoes and the intestinal barrier

1. Potatoes and the intestinal barrier Tutu S. Mzee Pathophysiologie-Seminar für Bioinformatiker 25.06.2004

2. Content • Significance of Potatoes world wide • What are Glycoalkaloids? • Study Introduction • Conclusion • What are IBD? • Discussion

3. Potatoesworldwide • 190 million tons of potatoes are produced in 180 countries worldwide. • Potatoes can be cultivated under various climatic conditions up to 4.500 m above sea level. • Potatoes are one of the global staple foods – 2/3 of the world population are reliant on potatoes.

4. PotatoContents Morgens rund Mittags gestampft Abends in Scheiben Dabei soll`s bleiben Es ist gesund (J. W. v. Goethe)

5. What are Glycoalkaloids? • Natural steroidal toxins present in potatoes (green potatoes) and other members of the Solanaceae plant family. • The two glycoalkaloids present in potatos • Alpha-Solanine • Alpha-Chaconine • Plants use Glycoalkaloids (GA) to defend themselves against fungi, bacteria, and other parasites

6. Structure of Chaconine Normal levels in potatoes 20-100 mg chaconine per kg of potatoes • Consist of a nonpolar lipophilic six-ring steroid aglycon nucleus with a nitrogen atom connecting the fifth and the sixth ring. • Polar water-soluble tri-saccharide sugar moiety at a 3-OH position α-chaconine

7. Structure of Solanine Normal levels 20-100 mg solanine per kg of potatoes, higher levels in green potatoes • Both have the same aglyconic stucture Soladine • They differ in their trisaccharides • Both inhibit acetyl-choline esterase • Can interfere with membrane structure/ function • Can cause leakage of cell content -solanine

8. Interactions of glycoalkaloids with cell membrane • GA align themselves parallel to the cholesterol • Lipophilic part of the GA forms a covalent complex with cholesterol • GA-cholesterol complex migrates into the membrane • The hydrophilic glyco-moiety protrudes away from the cell wall • The sugars compete for space • Membrane curves itself to minimize mutual interference • At high GA conc. the membrane bilayer disrupt

9. Potato Glycoalkaloids Adversely Affect Intestinal Permeability and Aggravate Inflammatory Bowel Disease Bijal Patel, Robert Schutte, Peter Sporns, Jason Doyle, Lawrence Jewel, and Richard N. Fedorak Inflammatory bowel disease 2002, 8(5): 340-346 Methods • Glycoalkaloids chaconine and solanine on cultured epithelia • In vitro experiment • In vivo experiment Materials • Homozygot IL-10 gene-deficient mice • T84 cell cultur monolayers • Normal control mice

10. Glycoalkaloids on Cultured Epithelia Procedure • Chaconine (0-20µM), Solanine (0-50µM) and a 1:1 Chaconine-to-Solanine mixture NOTE:A 1:1 Chaconine-to-Solanine mixture complies to the approx. ratio found in potatoes used for human consumption • T84 monolayere exposed to substances for a varying interval of time • Change in electrical resistance of monolayer was measured. Cell-Monolayer

11. Chaconine/solanine Chaconine solanine Effects of Glycoalkaloids on Cultured epithelia The injury (represented by change of epithelial resistance) caused by chachonine-to-solanine > chaconin alone >solanine alone

12. In Vitro Experiment • (Ussing chamber) • Procedure • 1:1 chaconine-to-solanine physiologic mixture (5µM) was • exposed to intact sheets of mammalian intestine • On intestine from normal control mice and on intestine from IL-10 gene-deficient mice with a genetically engineered IBD (inflammatory bowel disease) • In Vivo Experiment • (oral feeding) • Procedure • 1:1 chaconine-to-solanine mixture (3mg/kg/d) was fed orally via their drinking water for 21days • 3mg/kg/d represents,the daily amount consumed in a human diet (one plate of fried potato skins daily)

13. Effects of Glycoalkaloids on epithelia Small intestine (Ussing chamber) Large intestine (histologic score) • Mixture (chaconine/solanine) did not affect intestine from control mice • Mixture accentuated the histological injury seen in IL-10 deficient mice • and increases mannitol fluxes as a pattern of decreased barrier function

14. Conclusion • Glycoalkaloids permeate and disrupt epithelial barrier of cell culture monolayers and sheets of mammalian intestine. • Epithelial barrier of T84 monolayer disrupts in a dose-dependent fashion. • The membrane disruptive effect of a one-to-one mixture of solanine and chaconine was additive. • IL-10 gene-deficient mice demonstrated a greater disruption and inflammation, when exposed to glycoalkaloids. NOTE: Mechanical damage to potato tissues increases the concentration of glycoalkaloids available for consumption. Frying potatoes at high temperature preserves and concentrates glycoalkaloids (GA) within the potatoes. On boiling, glycoalkaloids are hydrolized and deactivated.

15. Inflammatory Bowel Disease The two important forms of IBD are Ulcerative colitis and Crohn`s disease • Both are chronic intestinal inflammatory diseases • Exact aethiopathology is still unknown. But imbalance of pro- and anti-inflammatory cytokines (e.g. Il-10) causes the main symptoms of the disease. • IBD is related to rheumatic diseases

16. Symptoms and Pathogenesis of IBD • Symptoms: • Diarrhea, at times with mucus and blood • Stomach aches • Stenosis or stricture of bowel (intestinal obstruction) • Affection of liver, joints, eyes and skin Surgical resection Pathogenesis of IBD

17. Nutrition in the aethiopathology of IBD • Till present there is no convincing evidence that eating habits or certain food contents are involved in the development of inflammatory bowel disease. • It is assumed, that the growing incidence of IBD (35-55 per 100,000 people) might be caused by the consumption of refined sugars, hardened fat and the low intake of dietary fiber. • Animal experiments showed that Carrageen(E 407), a thickening agent from red alga caused intestinal inflammation. But a pathogenic effect on humans has not been varified yet On the basis of the introduced study IBD patients should be notified that excessive consumption of „Country potatoes“ or the uptake of green potatoes could negatively affect their intestinal function.

18. Inflammatory bowel disease refers to the condition that results when cells involved in inflammation and immune response are called into the lining of the GI tract. This infiltration thickens the bowel lining and interferes with absorption and motility (the ability of the bowel to contract and move food). With abnormal ability to contract and abnormal ability to absorb, the bowel’s function is disrupted